The oxidative phosphorylation (OXPHOS) system: nuclear genes and human genetic diseases

The ubiquitous nature of mitochondria, the dual genetic foundation of the r espiratory chain in mitochondrial and nuclear genome, and the peculiar rule s of mitochondrial genetics all contribute to the extraordinary heterogenei ty of clinical disorders associated with defects of oxidative phosphorylati on (mitochondrial encephalomyopathies). Here, we review recent findings abo ut nuclear gene defects in isolated OXPHOS enzyme complex deficiency. This information should help in identifying patients with mitochondrial disease and defining a biochemical and molecular basis of the disorder found in eac h patient. This knowledge is indispensable for accurate genetic counseling and prenatal diagnosis, and is a prerequisite for the development of ration al therapies, which are still, at present, woefully inadequate. (C) 2001 Jo hn Wiley & Sons, Inc.